Percocet is one of the most recognized prescription pain medications in the United States — a combination of oxycodone (an opioid) and acetaminophen (a non-opioid pain reliever and fever reducer). For decades, it has been one of the most commonly prescribed analgesics for moderate to severe acute pain, and it remains widely used despite growing awareness of the opioid epidemic and significant prescribing restrictions implemented over the past decade.
What Is Percocet?
Percocet is a brand-name combination analgesic containing oxycodone hydrochloride and acetaminophen. It is manufactured by Endo Pharmaceuticals and available in four strengths, all containing the same amount of acetaminophen (325 mg) but varying amounts of oxycodone: 2.5/325 mg, 5/325 mg, 7.5/325 mg, and 10/325 mg. Generic oxycodone/acetaminophen tablets are widely available at significantly lower cost.
Other brand names for oxycodone/acetaminophen combinations include Roxicet (oral solution) and various generics. Percocet should not be confused with:
- OxyContin — extended-release single-ingredient oxycodone (no acetaminophen)
- Roxicodone — immediate-release single-ingredient oxycodone (no acetaminophen)
- Percodan — oxycodone combined with aspirin instead of acetaminophen (now rarely used)
How Percocet Works
Percocet's two components work through completely different mechanisms, which is why the combination is more effective than either alone at the same doses:
Oxycodone (Opioid Component)
Oxycodone is a semi-synthetic opioid derived from thebaine. It binds to mu-opioid receptors in the brain, spinal cord, and peripheral tissues to produce analgesia, euphoria, and sedation. It also activates kappa and delta opioid receptors. Oxycodone has approximately 1.5 times the analgesic potency of morphine by weight, with an oral bioavailability of 60–87% — substantially higher than morphine's 20–40%. It is metabolized by CYP3A4 (to inactive noroxycodone) and CYP2D6 (to the more potent oxymorphone), and has a half-life of approximately 3–4 hours for immediate-release forms.
Acetaminophen (Non-Opioid Component)
Acetaminophen (paracetamol) provides analgesia and antipyretic (fever-reducing) effects through mechanisms that are still not completely understood but involve inhibition of prostaglandin synthesis in the CNS, activation of endocannabinoid pathways, and modulation of serotonin pathways. It does not have anti-inflammatory properties at standard doses and does not work through opioid receptors. By combining acetaminophen with oxycodone, Percocet achieves better pain relief than either drug alone with lower opioid doses — an approach called "opioid-sparing."
Medical Uses of Percocet
- Post-surgical pain: Orthopedic, dental, abdominal, thoracic, and other surgeries; most commonly as short-term post-operative analgesia
- Acute injury pain: Fractures, dislocations, significant soft tissue trauma
- Dental pain: Post-extraction and post-procedure pain management
- Cancer pain: Moderate severity cancer pain, often as part of a multimodal regimen
- Acute severe medical pain: Kidney stones, acute back pain exacerbations, sickle cell crisis
Percocet is not indicated for chronic non-cancer pain as a first-line treatment. Current CDC guidelines recommend exhausting non-opioid and non-pharmacological treatments before considering opioids for chronic pain conditions.
Percocet Dosage
| Strength | Oxycodone / APAP | Typical Adult Dose | Max Frequency |
|---|---|---|---|
| Percocet 2.5/325 | 2.5 mg / 325 mg | 1–2 tablets every 6 hrs | Max APAP 4,000 mg/day |
| Percocet 5/325 | 5 mg / 325 mg | 1 tablet every 6 hrs | Max APAP 4,000 mg/day |
| Percocet 7.5/325 | 7.5 mg / 325 mg | 1 tablet every 6 hrs | Max APAP 4,000 mg/day |
| Percocet 10/325 | 10 mg / 325 mg | 1 tablet every 6 hrs | Max APAP 4,000 mg/day |
Dosing should be reduced in elderly patients, patients with renal or hepatic impairment, and those taking CNS depressants. The lowest effective dose for the shortest duration necessary is the guiding principle.
Side Effects of Percocet
From Oxycodone (Opioid Component)
- Constipation — universal; does not improve with time; requires bowel management
- Nausea and vomiting
- Sedation and drowsiness
- Dizziness
- Respiratory depression — most dangerous; the primary cause of opioid overdose death
- Euphoria and mood changes — contributing to addiction potential
- Itching (pruritus)
- Physical dependence and addiction risk
From Acetaminophen Component
- Rare at therapeutic doses
- Hepatotoxicity — severe liver damage or acute liver failure with overdose or chronic excessive use
- Rare but serious skin reactions (Stevens-Johnson Syndrome)
- Thrombocytopenia (rare)
Percocet vs OxyContin: Key Differences
| Feature | Percocet (Oxycodone + APAP) | OxyContin (Extended-Release Oxycodone) |
|---|---|---|
| Formulation | Immediate-release combination | Extended-release single-ingredient |
| Duration of action | 4–6 hours | 8–12 hours |
| Acetaminophen | Yes (325 mg per tablet) | No |
| Approved use | Moderate to severe acute pain | Around-the-clock severe pain (opioid-tolerant) |
| Abuse deterrent | No | Yes (newer formulations) |
| Max daily dose consideration | Limited by acetaminophen (4,000 mg/day) | Limited by opioid tolerance and clinical need |
Drug Interactions
- Benzodiazepines and alcohol — life-threatening respiratory depression (FDA Black Box Warning)
- CYP3A4 inhibitors (ketoconazole, erythromycin, ritonavir) — increase oxycodone blood levels; risk of toxicity
- CYP3A4 inducers (rifampin, carbamazepine, phenytoin) — reduce oxycodone levels; may cause withdrawal or loss of pain control
- MAO inhibitors — potentially fatal interaction; contraindicated within 14 days
- Other CNS depressants — additive respiratory depression
- Warfarin — acetaminophen component may enhance anticoagulant effect at higher doses
- Other acetaminophen-containing products — inadvertent overdose risk